Innate immune responses in primary HIV-1 infection

Abstract

Purpose of review: Events occurring in acute HIV-1 infection are now recognized to be critical determinants of the subsequent disease course. Innate responses constitute the first line of defence against pathogens, and also play a key role in triggering the early adaptive response; as such, the innate responses activated in acute HIV-1 infection and their contribution to control of viral replication or disease pathogenesis are the focus of much current research. We review recent advances in this area.

Recent findings: Dendritic cell subsets can play pleiotropic roles in acute HIV-1 infection, with in-vitro studies illustrating that HIV-dendritic cell interactions may have outcomes as diverse as virion destruction, virus dissemination, T-cell triggering or subversion of dendritic cell functions. Natural killer cells can be activated in acute HIV-1 infection, and mounting evidence suggests that they contribute to determining the ensuing course of disease; however, much remains to be learned about how they mediate their effects.

Summary: The importance of innate responses as determinants of the outcome of HIV infection is increasingly evident, but more work is needed to understand how innate immunity can be harnessed to combat this infection.

Figure 1. Pleiotropic functions of dendritic cell (DC) subsets in response to HIV encounter

The figure illustrates the range of effects that HIV has on conventional CD11c⁺ myeloid dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs) and their potential consequences. APOBEC, apolipoprotein B mRNA editing enzyme catalytic polypeptide; IFN, interferon; IL, interleukin; NK, natural killer; TNF, tumor necrosis factor.

Figure 2. Diagram to illustrate some of the putative interactions between ligands on (a) an uninfected cell and (b) an HIV-infected cell and activating/inhibitory natural killer (NK) cell receptors

The signals NK cells receive following interaction with uninfected cells are likely to be predominantly inhibitory (−); but on HIV-infected cells expression of ligands for inhibitory NK cell receptors is postulated to be reduced, whilst ligands for activating NK cell receptors are thought to be induced, resulting in many NK cells receiving a greater proportion of activating (+) signals and hence being triggered into functional activity.